Diacetyl, a reactive diketone used in artificial butter flavoring has been associated with obliterative bronchiolitis (OB) in employees at microwave popcorn packaging plants; however, the mechanisms of toxicity are unknown. We recently demonstrated that diacetyl, the major volatile component of artificial butter flavoring, caused OB-like lesions in rats after inhalation exposure. Because of concerns about diacetyl toxicity, it is being replaced in some consumer products by 2,3-pentanedione (PD), and possibly 2,3-hexanedione (HD), both structurally-related and untested chemicals. Because the toxicity of inhaled PD and HD are unknown, studies were conducted to characterize the toxicity after inhalation exposure to a range of concentrations in rodents. Male and female Wistar-Han rats were exposed to 0, 50, 100, or 200 ppm PD 6h/d, 5d/wk for up to 2 wk. PD was found to cause OB-like lesions simlar to those caused by diacetyl. The epithelium lining the respiratory tract was the site of toxicity in all rats exposed to 200 ppm. Diacetyl and PD both caused fibrotic airway lesions in rats with pathological features of OB. The histopathological and biological changes observed in rats raise concerns that PD inhalation may also cause OB in exposed humans.nalyzed for cytokines at various timepoints during exposure. Additional studies are underway to investigate the time course of events leading to airway fibrosis, in order to find areas for potential intervention and treatment. HD toxicity is being investigated using the same study design.